Effects of ethanol on receptor-mediated endocytosis in the liver

Ethanol administration impairs multiple aspects in the process of receptor- mediated endocytosis (RME) in the liver. Studies from our laboratory over t he last 10 years have carefully examined RME by the hepatocyte specific asi aloglycoprotein receptor (ASGP-R). We have identified a time course for eth anol-induced defects in RME and established that many of the impairments oc cur initially in the centrilobular region of the liver and as early as one week after ethanol administration. Impaired intravesicular acidification in ethanol-fed animals has been identified, and these defects in acidificatio n could alter multiple protein trafficking pathways including RME. In addit ion to altered acidification, altered receptor function (including receptor inactivation) could also contribute to impaired trafficking. Current studi es in our laboratory are aimed at an examination of posttranslational modif ications in the receptor (acylation and phosphorylation) that are known to affect its function. A role for the ASGP-R in the process of alcoholic apop tosis is also being examined because proper functioning of the ASGP-R is th ought to be important in clearance of apoptotic cells. (C) 1999 Elsevier Sc ience Inc. All rights reserved.